For Many Men With Prostate Cancer, It's the Weak Link: The Needle Biopsy

"It's just as important as getting a second opinion for surgery or radiation. You could have the best surgeon in the world, but if you don't have the right pathology, you could have the wrong thing done for you."

Just a few tiny cores of tissue, and a man's life may depend on what you have to say about it. You make the call: Your word is, for all practical purposes, the Gleason score, your opinion a huge part of the treatment decision-making. So think, think -- what about those funny looking cells over there? Is it cancer?

The prostate biopsy can be a pathologist's worst nightmare. "Of all biopsies, prostate biopsies are probably the hardest" explains pathologist Jonathan Epstein, M.D., who is world-renowned for his expertise and accuracy in judging prostate cells, and has probably examined more prostate tissue than any other pathologist. "You're dealing with such a limited amount of tissue, and cancers tend to creep around the benign gland," rather than forming as a solid mass. Imagine a Tootsie Roll, wrapped in paper. The cancer is like the paper, a veneer over an expanse of healthy tissue. And the veneer is often maddeningly ambiguous. So not only can the hollow-core biopsy needle overshoot and miss the cancer, the cancer cells it does get don't always match the pictures in the textbook.

One result of this is the biopsy labeled "atypical" -- a diagnosis that appears in about 5 percent of biopsies at most institutions, says Epstein. "Basically, what that means is that a pathologist will see something that he thinks could be cancer, but is not comfortable calling it cancer." For many patients, the next step is having a repeat biopsy--and the value of this is often questionable, says Epstein. "The problem is, in about 20 percent of cases, the biopsy can miss cancer -- so even if it's negative, it doesn't mean the patient doesn't have cancer; in fact, the cancer can be extensive. We've seen some missed entirely. They were called totally benign, yet they were cancer."

A repeat biopsy might be a reasonable option if no cancer is found, he adds, "but if there is already a diagnosis of cancer, or even 'atypical cells,' a repeat biopsy may just lead to more confusion."

Another problem Epstein has found is that many pathologists seem just as likely to over-diagnose cancer: "There are many mimickers of prostate cancer under the microscope, and people not as familiar with prostate biopsies can diagnose cancer when it's not." About one and a half percent -- 6 to 8 men -- of the patients who come to the Brady Urological Institute each year with a diagnosis of prostate cancer are found to have been misdiagnosed. "We switch the diagnosis. We say, 'This is not cancer, this is benign."'

Perhaps the best option in the case of tricky diagnoses, says Epstein, is to have the slides sent to an expert. "About 70 to 80 percent of the time, it can be resolved as being definitively benign, or definitely cancer." But even biopsies that seem straightforward deserve another look. "We recommend getting a second opinion before anybody undergoes any form of treatment", says Epstein. "It's just as important as getting a second opinion for surgery or radiation. You could have the best surgeon in the world, but if you don't have the right pathology, you could have the wrong thing done for you."

On this point, Epstein is blunt: "We have done numerous studies showing the reproducibility of Gleason scores in the general pathology community, " looking at the Gleason grade based on a biopsy, and then comparing it to the actual specimen removed during surgery, "and found that by and large, the Gleason grading that's performed is disappointing. All across the map, it doesn't correlate with what you see in a radical prostatectomy. People are having decisions made -- surgery or radiation, or watchful waiting -- based in part on a Gleason grade, when it's not accurate at all."

Beware the low-grade Gleason score: Particularly erroneous, Epstein has found, are biopsies given low Gleason scores. "From the standpoint of patient care, the low-grade Gleason (a score of 2,3, or 4) doesn't exist, and it gives a false sense of optimism. Even if I call something a 2-4 in a biopsy, when the prostate is removed in a radical prostatectomy, it will turn out to be Gleason 5,6 or higher." Low-grade Gleason tumors do exist, Epstein says, "but where they exist is in the central transition zone of the prostate, not in the peripheral zone where you do biopsies. A low Gleason score is the kind of thing that shows up more in a transurethral resection of the prostate" (TURP), a procedure used to treat prostate enlargement, in which tiny bits of tissue from the center of the prostate are chipped away and removed through the urethra. "If a tiny focus of low-grade cancer shows up on a TURP, it's not as worrisome as a tiny bit of intermediate tumor found on a biopsy. A low-grade Gleason score is valid on a TURP, but not on a needle."

An on-line course for pathologists: In an effort to improve prostate cancer diagnosis, Epstein is teaching pathologists in a tutorial he devised for the Internet -- a website for pathologists. "We just did it on our own," he explains, "because we think pathologists can do better than they have been. The key is education, not just getting frustrated." Epstein and colleagues have tried other approaches such as articles, he says, but have found that this website is "an amazing tool, because it can reach so many people quickly." The on-line course -- the first of its kind -- takes about an hour. First, pathologists are asked to grade a set of biopsies. Then, they're shown some of the telltale signs of various grades-Epstein calls them "tricks of grading"-and taught how to interpret another set of biopsies. Finally, they are asked to re-evaluate the biopsies. "We've found that pathologists can make a dramatic improvement, just in this brief tutorial." Pathologists interested in learning more can find the website at: www.pathology.jhu.edu/